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Báo cáo y học: "Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. | Perez-Bercoff et al. Retrovirology 2010 7 98 http www.retrovirology.eom content 7 1 98 RETROVIROLOGY RESEARCH Open Access Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir Danielle Perez-Bercoff1 Perrine Triqueneaux2 Christine Lambert1 Aboubacar Alassane Oumar3 Anne-Marie Ternes1 Sounkalo Dao3 Patrick Goubau2 Jean-Claude Schmit1 and Jean Ruelle2 Abstract Background Human Immunodeficiency Virus type 2 is naturally resistant to some antiretroviral drugs restricting therapeutic options for patients infected with HIV-2. Regimens including integrase inhibitors INI seem to be effective but little data on HIV-2 integrase IN polymorphisms and resistance pathways are available. Materials and methods The integrase coding sequence from 45 HIV-2-infected INI-naive patients was sequenced and aligned against the ROD group A or EHO group B reference strains and polymorphic or conserved positions were analyzed. To select for raltegravir RAL -resistant variants in vitro the ROD strain was cultured under increasing sub-optimal RAL concentrations for successive rounds. The phenotype of the selected variants was assessed using an MTT assay. Results We describe integrase gene polymorphisms in HIV-2 clinical isolates from 45 patients. Sixty-seven percent of the integrase residues were conserved. The HHCC Zinc coordination motif the catalytic triad DDE motif and AA involved in IN-DNA binding and correct positioning were highly conserved and unchanged with respect to HIV-1 whereas the connecting residues of the N-terminal domain the dimer interface and C-terminal LEDGF binding domain were highly conserved but differed from HIV-1. The N155 H INI resistance-associated mutation RAM was detected in the virus population from one ARV-treated INI-naive patient and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively. No other known INI RAM was detected. Under RAL selective pressure in vitro a ROD variant carrying the Q91R I175M .